Asymmetric cell division is a basic mechanism for generating cellular diversity. C. crescentus has proven a genetically and biochemically tractable bacterium in which asymmetric cell division and differentiation can be studied. The "stalked" form of C. crescentus divides, much like a stem cell, to produce the old stalked cell and a new motile "swarmer" cell at each division (A->A+B). Two-component and phosphorelay signal transduction systems are commonly found to play central roles in the regulation of cell growth, division and differentiation. C. crescentus contains a relatively large number of histidine protein kinases (HPK) and response regulators (RR) compared to other organisms with similarly sized genomes. The activities of a number of these signal transduction proteins are temporally and spatially regulated to link regulation of developmental changes with progression through the cell cycle. The main objective of the proposed experiments is to study the interactions of two HPKS, PleC and DivJ, with their cognate RR, DivK, in order to define the specificity of this interaction at the molecular and atomic levels and understand the potential regulatory implications of this interaction. This work will serve to help us better understand how two different histidine kinases, PleC and DivJ, interact with the same response regulator to determine daughter cell fate.